Effects of vasoactive agents on uptake of immunoglobulin G complexes by mesangial cells
Singhal, P.C.; Santiago, A.; Satriano, J.; Hays, R.M.; Schlondorff, D.
American Journal of Physiology 258(3 Pt 2): F589-F596
1990
ISSN/ISBN: 0002-9513 PMID: 2156448 Document Number: 358000
Mesangial handling of immune complexes may be important in immune injury. We examined whether vasoactive agents, independent of hemodynamic effects, could directly influence uptake of immunoglobulin G (IgG) complexes by mesangial cells (MC). Under basal conditions, MC took up more gold particles coated with IgG2b (P < 0.05) than coated with IgG2a. Preincubation of MC with angiotensin II (ANG II) (5 .times. 10-7 M) resulted in enhancement of uptake (P < 0.05) of IgG2b-gold [7,578 .+-. 968 counts per minute (cpm) per well], IgG2a-gold (4,566 .+-. 295 cpm/well; P < 0.05) when compared with respective controls (IgG2b-fold, 5,513 .+-. 762 cpm/well; IgG2a-gold, 3,282 .+-. 439; BSA-gold, 2,279 .+-. 97). Cytochalasin B produced a significant reduction of uptake of IgG2b-gold (2,224 .+-. 88 cpm/well) when compared with the uptake by control cells (3,711 .+-. 287 cpm/well) (P < 0.05). Pretreatment of MC with atrial natriuretic peptide (ANP, 10-9 M) slightly decreased uptake of IgG-fold under basal conditions (P < 0.05) and decreased the response to ANG II (P < 0.05). Similarly, dopamine (DA, 10-6 M) attenuated uptake of IgG2b-gold under basal (P < 0.01) as well as ANG II-stimulated (P < 0.01) states. ANP increases mesangial guanosine 3',5'-cyclic monophosphate (cGMP), DA, adenosine 3',5'-cyclic monophosphate (cAMP) content. Direct addition of dibutyryl adenosine 3',5'-cyclic monophosphate (5 .times. 10-4 M) reduced IgG-gold uptake (2,239 .+-. 276 cpm/well) when compared with control (3,622 .+-. 59 cpm/well) and also antagonized the uptake (P < 0.001) under ANG II-stimulated condition. Similarly, dibutyryl guanosine 3',5'-cyclic monophosphate (5 .times. 10-4 M) decreased uptake of IgG2b-gold under basal (P< 0.001) as well as ANG II-stimulated (P < 0.01) states. Our study indicates that ANG II, ANP, and DA may, in addition to their hemodynamic effects, also directly influence the handling of macromolecules by MC.